Effects of smoking on drug action.

Abstract

The effects of smoking on drug metabolism in 3 categories of cigarette smokers (nonsmokers, light smokers, and heavy smokers) were studied in patients in 22 hospitals in 7 countries in a collaborative program. The data collected by monitors along with a smoking history on consecutively admitted patients were recorded on self‐coding forms. Details were obtained on all drugs administered, and the judgment of efficacy by the prescribing physician was included. Propoxyphene was rated ineffective in 10% of nonsmokers, 15% of light smokers, and 20% of heavy smokers, the difference being statistically significant (p < 0.01). Among 835 recipients of the drug, the most common diagnoses were chronic obstructive lung disease, musculoskeletal disorders, and neoplastic diseases. Decreasing age, male sex, race other than white, and ingestion of large amounts of alcohol were other factors positively related to smoking. In patient~ receiving diazepam and chlordiazepoxide, the frequency of drowsiness was highest in nonsmokers, intermediate in light smokers, and lowest in heavy smokers. The differences among the comparison groups by chi‐square tests were statistically significant for diazepam (p < 0.05) and for chlordiazepoxide (p < 0.02). Phenobarbital data gave no evidence of an association between cigarette smoking and drowsiness attributed to the drug (p > 0.05). The relation between cigarette smoking and the benzodiazepines was evident at all dose levels; drowsiness was less common in smokers regardless of sex. The relation with smoking held for each of the diagnoses (chronic obstructive lung disease, cirrhosis of the liver, and lung cancer), and an inverse relation between drowsiness and alcohol consumption was evident at all levels of alcohol intake. Among recipients of chlorpromazine in a psychiatric population, drowsiness was highest in nonsmokers, intermediate in light smokers, and lowest in heavy smokers. Drowsiness was dose‐related but not related to smoking status; alcohol consumption correlated strongly with smoking habits and drowsiness was more frequent among nonsmokers than among light and heavy smokers in each category of alcohol consumption. The data are compatible with the hypothesis that substances in cigarette smoke induce liver microsomal enzymes which increase the metabolism of these drugs.